US4721800A - Biocompatible surfaces - Google Patents

Biocompatible surfaces Download PDF

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Publication number
US4721800A
US4721800A US06/778,185 US77818585A US4721800A US 4721800 A US4721800 A US 4721800A US 77818585 A US77818585 A US 77818585A US 4721800 A US4721800 A US 4721800A
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group
sup
compound
formula
mixture
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US06/778,185
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Inventor
Dennis Chapman
Aziz A. Durrani
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Abbott Vascular Devices Ltd
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Biocompatibles Ltd
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Assigned to BIOCOMPATIBLES LTD. reassignment BIOCOMPATIBLES LTD. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: CHAPMAN, DENNIS, DURRANI, AZIZ A.
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Publication of US4721800A publication Critical patent/US4721800A/en
Priority to US07/789,894 priority Critical patent/US5229162A/en
Priority to US08/169,641 priority patent/US5380904A/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C07F9/65844—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a five-membered ring which may be condensed with another ring system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0076—Chemical modification of the substrate
    • A61L33/0082—Chemical modification of the substrate by reacting with an organic compound other than heparin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/30—Compounds having groups
    • C07C43/315—Compounds having groups containing oxygen atoms singly bound to carbon atoms not being acetal carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl

Definitions

  • This invention relates to biocompatible surfaces and to new compounds useful in the production of such surfaces.
  • Heart valves and blood vessel prostheses, balloon pumps and catheters are being implanted in daily surgical practice to restore or diagnose cardiovascular function.
  • Artificial organs are routinely employed in blood detoxification by absorptive haemoperfusion and in oxygenation (membrane oxygenators and heart-lung devices). Considerable effort and capital is invested in Europe and the U.S.A. in the development and experimental evolution of an implantable artificial heart system.
  • the devices are generally constructed from polymeric materials and when in use, a blood-polymer contact is present.
  • Biological membranes are important in all areas of the body. Every cell has an outer membrane and within the cell there are membranes that act to compartmentalise the various organelles, e.g. the mitochondria, nucleus and endoplasmic reticulum. Membranes are particularly important features of the blood cells, e.g. erthrocytes and leucocytes.
  • the various cell membranes, including those of red blood cells, are all built upon an asymmetric lipid matrix of polar lipids in which the intrinsic proteins are distributed.
  • the outer surface of the lipid matrix consists of both phosphatidyl choline lipids and sphingomyelin lipids. Both of these classes of lipid have the same polar group: ##STR3##
  • This polar surface is a common feature of the outer surface of red blood cells, platelets, lymphocytes, etc.
  • the inner surface is different and usually contains a predominance of the negatively charged lipids.
  • the aim is chemically to modify some existing materials so that covalent linkages are formed containing these polar groups. This retains the mechanical properties of the material whilst the interfacial properties are changed to mimic those of membrane surfaces.
  • New compounds of the present invention are those of the formula: ##STR4## in which X 1 is a reactive group that can react to form a covalent bond with a reactive group on the surface of a material to be rendered biocompatible, X 2 is a group --O.sup. ⁇ or a precursor of such a group, n is 2, 3 or 4, Y is a group --N.sup. ⁇ R 3 A.sup. ⁇ wherein each R, which may be the same or different, is a C 1 -C 4 alkyl group and A.sup. ⁇ is an anion present when X 2 is an electrically neutral group or Y is ##STR5## wherein R 1 together with X 2 forms a direct bond between the nitrogen and the phosphorus atoms.
  • each R represents methyl and that n is 2 so that a phosphatidylcholine residue is introduced onto the surface but analogues and homologues of phosphatidylcholine of the type defined can equally well be introduced. Alternatively, or preferably in combination therewith, a phosphatidyl ethanolamine-type residue is introduced onto the surface.
  • X 1 will depend upon the chemical nature of the reactive group on the surface to be rendered biocompatible. Almost all surfaces that one might wish to render biocompatible normally contain free reactive alcoholic hydroxy groups on their surface or are surfaces onto which such free alcoholic hydroxy groups can be readily introduced, e.g. using an alkali metal hydroxide to hydrolyse a surface ester group or halogeno group. Consequently, X 1 will normally be a group that will react with an alcoholic hydroxy group to form a covalent link, typically by forming a phosphonic acid ester group from the alcoholic hydroxy group and the phosphonic acid residue of the phosphatidylcholine- or phosphatidyl ethanolamine-type material. Such phosphonic ester groups can be prepared from compounds of the invention in which X 1 represents halogen, particularly chlorine although, depending upon the reactivity of the alcoholic hydroxy group, other halogens such as fluorine or bromine can also be used.
  • X 1 may also represent a group of the formula: ##STR6## each R, which may be the same or different, represents a C 1 -C 4 alkyl group, preferably both methyl, and X 3 represents a group that will react with the reactive group on the surface to be rendered biocompatible with the formation of a covalent linkage.
  • X 3 will depend upon the nature of the reactive group on the surface to be rendered biocompatible but, for the reasons mentioned above, the reactive group on the surface to be rendered biocompatible will normally be an alcoholic hydroxy group, and, again as mentioned above, this indicates that the group X 3 will conveniently be a halogeno group, typically chlorine although again, depending upon the reactivity of the alcoholic hydroxy group, other halogens such as fluorine or bromine can be used.
  • halogeno group typically chlorine although again, depending upon the reactivity of the alcoholic hydroxy group, other halogens such as fluorine or bromine can be used.
  • X 1 can represent a group of the formulae: ##STR7## where y is an integer of 1 to 10 and R and X 3 are as defined above.
  • the group X 2 will normally be -- O.sup. ⁇ so that the modified surface carries a phosphatidylcholine- or phosphatidyl ethanolamine-type residue but it is often convenient to have the group X 2 in the new compounds of the invention representing a precursor of the -- O.sup. ⁇ group, e.g. halogen such as chlorine so that this precursor group is converted to -- O ⁇ before, during or after formation of the covalent linkage by the reaction of the group X 1 .
  • halogen such as chlorine
  • Anion A.sup. ⁇ when required to be associated with the new compounds of the invention can be any anion, preferably a biocompatible anion.
  • This anion can be the anion of an inorganic or organic acid and is typically a halide anion such as chloride or alternatively the anion of an alkanoic acid such as acetic acid.
  • the new compounds of the invention can be prepared by reacting a compound of the formula:
  • a phosphorus oxyhalide e.g. POCl 3 to give compounds of the formula I in which X 1 represents halogen and, when Y is a group --N.sup. ⁇ R 3 .A.sup. ⁇ , X 2 is also halogen.
  • Analogues of phosphorus oxyhalides may be used in order to produce derivatives of formula I in which X 1 and X 2 represent other reactive groups or alternatively, reaction can first be carried out with phosphorus oxyhalide to give a dihalophosphate and one or both of the halogeno residues can subsequently be converted by methods known per se into other reactive groups so that X 1 can react with the reactive group on the surface to be rendered biocompatible with the formation of the covalent link.
  • Compound VIII is prepared by reacting I with an ethyl vinyl ether mono protected diols of formula: ##STR11## followed by removal of the protective group with acidified ice water, concentration and sodium bicarbonate treatment.
  • All the compounds of the invention will react with hydroxy groups in the surface to be rendered biocompatible to bind the phosphatidylcholine- or phosphatidyl ethanolamine-type covalently to the surface except compounds of the invention where X 1 is a group of formula III or V which will react with surface halogens and acid chloride groups respectively. In all cases the phosphatidylcholine- or phosphatidyl ethanolamine-type group becomes covalently linked to the surface.
  • a process for rendering a surface biocompatible which comprises applying to the surface a compound of formula I under conditions such that the group X 1 reacts to form a covalent linkage with a reactive group on the surface to be rendered biocompatible.
  • the compounds of the invention are not very soluble in solvents such as chloroform, petroleum ether, carbon tetrachloride or tetrahydrofuran and tend to react with solvents in which they are appreciably soluble, e.g. water or alkanols, so that it is preferred to use the compounds in undiluted state for the treatment of the surfaces.
  • solvents such as chloroform, petroleum ether, carbon tetrachloride or tetrahydrofuran
  • the present invention is applicable in principle to the treatment of the surface of any prosthesis to be introduced into the human or animal body or any surface which is to be brought into contact with body fluids, e.g. blood on an extra-corporeal basis, cells or tissues in culture. It may also be advantageous to treat surfaces of equipment, especially culture vessels, used in cell and tissue culture, in order to provide biocompatible surfaces.
  • body fluids e.g. blood on an extra-corporeal basis, cells or tissues in culture.
  • body fluids e.g. blood on an extra-corporeal basis, cells or tissues in culture.
  • surfaces of equipment especially culture vessels, used in cell and tissue culture, in order to provide biocompatible surfaces.
  • surfaces of other materials such as metals, or plastics which are polymers or copolymers based on various polyacrylic or polyvinyl materials and others containing olefinic bonds are also suitable for modification, if necessary after replacing the double bonds by, for example, halogeno, hydroxy or acid chloride groups, in accordance with the present invention.
  • Phosphorus oxychloride (23 g; 0.15 mole) was dissolved in anhydrous carbon tetrachloride (50 ml), placed in a bath containing ice/salt mixture and was treated with a dropwise addition of acetylcholine (16.3 g; 0.1 mole) over 30 minutes. During this addition, a slow stream of dried nitrogen was passed through the mixture, which was stirred thoroughly throughout the reaction time. After the addition of acetylcholine, the mixture was stirred for an additional hour at 0° C. with continuous nitrogen passage.
  • the upper layer of the reaction mixture was collected, washed once with anhydrous carbon tetrachloride (50 ml) and was then freed from the volatile matter (40° C., 15 mm Hg) to obtain the yellow oil (I)(a) in more than 70% yield.
  • the substance was highly reactive towards water with the evolution of hydrogen chloride and gradually decomposed on standing but can be stored for up to 3 weeks under dry nitrogen in an air-tight glass container.
  • Ethylene glycol phosphatidylcholine (I)(c) (5.67 g; 0.025 mole) was dissolved in anhydrous absolute alcohol (25 ml), stirred and was treated with thallous ethoxide (6.22 g; 0.025 mole).
  • thallous ethoxide (6.22 g; 0.025 mole).
  • a white instantaneous precipitate was formed which was found to be very sparingly soluble in the solvent used. It was also found to be insoluble in acetronitrite and benzene. The substance decomposed and dissolved in water.
  • Ethylene glycol phosphatidylcholine (I)(c) (22.7 g; 0.1 mole) was added dropwise into thoroughly stirred dichlorodimethylsilane (129 g; 1.0 mole). External cooling was applied to keep the temperature at about 20° C. The addition was completed in 30 minutes and the stirring was continued for another 30 minutes after which the mixture was freed from all volatile components (40° C.; 15 mm Hg) to obtain (I)(e) as dirty greyish gelatinous viscous liquid. The substance reacted with water with the evolution of hydrochloric acid.
  • a thin film of compound (I)(a) was applied to the materials named above. They were placed in a desiccator over P 2 O 5 for up to 5 minutes after which the excess of the reagent was washed off with water followed by ethanol and sodium bicarbonate solution (5% w/v). They were washed with water again followed by alcohol and dried with warm air.
  • Treated polyvinyl alcohol, polyhema and celluslose acetate sheet gave positive ESCA analysis for phosphorus and nitrogen.
  • the glass beads gave positive phosphate determinations by using untreated beads as reference.
  • Cellulose acetate and glass beads gave positive ESCA for phosphorus and nitrogen.
  • Substance (I)(a) is superior to substances (l)(b) and (I)(e) when organic materials are required to be treated.
  • the stability of the chemical bond obtained when (I)(a) is reacted with C--OH group is superior in stability and resembles those which occur naturally (for example in glycerophosphatidylcholine (GPC)).
  • GPC glycerophosphatidylcholine
  • the type of linkage (C--O--Si) obtained when (I)(b) and (I)(e) are treated with an organic OH group is less stable to hydrolysis.
  • compounds (I)(b) and (I)(e) are superior to (I)(a) when treatment of glass is required.
  • the bond (Si--O--P) is susceptible to hydrolysis when (Ia) is used to treat glass surfaces.
  • Perspex surface was hydrolysed by stirring perspex pieces in 40% w/v aqueous KOH at 80° C. for 12 hours. Neutralisation of the above treated perspex with dilute hydrochloric acid generated free --COOH groups on the surface. These pieces were then placed in thionyl chloride for up to 5 seconds and while still wet with thionyl chloride, were dropped in a flask containing (I)(f). The contents of the flask were mixed thoroughly and the plastic pieces were recovered, washed with hot methanol, water and methanol again and dried in warm air.
  • Phosphorus oxychloride 60 g; 0.39 mole was diluted with anhydrous tetrahydrofuran (100 ml) cooled (0° C.) and treated with a dropwise addition of triethylamine (25 g) with vigorous stirring over 30 minutes. A gentle stream of dried nitrogen was passed through the stirred mixture, and with the temperature still maintained at 0° C. the mixture was treated with small drops of ethanolamine (23.92 g; 0.39 mole) over 30 minutes and then stirred for an additional one hour. Volatile matter was distilled (40° C.; 15 mm Hg) and the gumlike dark orange semisolid was extracted with dried nitromethane (4 ⁇ 40 ml). The nitromethane extract was concentrated free from the solvent (50° C.; 15 mm Hg) to obtain the required substance as dark red oil which was highly reactive towards water.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Treatments Of Macromolecular Shaped Articles (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Peptides Or Proteins (AREA)
US06/778,185 1984-01-20 1985-01-18 Biocompatible surfaces Expired - Fee Related US4721800A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US07/789,894 US5229162A (en) 1984-01-20 1991-11-12 Article having biocompatible surface
US08/169,641 US5380904A (en) 1984-01-20 1993-12-20 Process for rendering a surface biocompatible, and articles containing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8401534 1984-01-20
GB848401534A GB8401534D0 (en) 1984-01-20 1984-01-20 Biocompatible surfaces

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US11476287A Division 1984-01-20 1987-10-29

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US06/778,185 Expired - Fee Related US4721800A (en) 1984-01-20 1985-01-18 Biocompatible surfaces
US07/328,709 Expired - Fee Related US4937369A (en) 1984-01-20 1989-03-27 Analogues of phosphatidylcholine or phosphatidyl ethanol amines
US07/510,840 Expired - Fee Related US5091551A (en) 1984-01-20 1990-04-18 Trialkyl-O-(W-aminoalkyl)-phosphatidylalkylammonium salts useful for the manufacture of biocompatible surfaces

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US07/328,709 Expired - Fee Related US4937369A (en) 1984-01-20 1989-03-27 Analogues of phosphatidylcholine or phosphatidyl ethanol amines
US07/510,840 Expired - Fee Related US5091551A (en) 1984-01-20 1990-04-18 Trialkyl-O-(W-aminoalkyl)-phosphatidylalkylammonium salts useful for the manufacture of biocompatible surfaces

Country Status (7)

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US (3) US4721800A (fr)
EP (1) EP0157469B1 (fr)
JP (5) JPH0631273B2 (fr)
AT (1) ATE43602T1 (fr)
DE (1) DE3570673D1 (fr)
GB (1) GB8401534D0 (fr)
WO (1) WO1985003295A1 (fr)

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US5217743A (en) * 1992-02-07 1993-06-08 Paradigm Biotechnologies Partnership Biomaterials of enhanced biocompatibility
US5342621A (en) * 1992-09-15 1994-08-30 Advanced Cardiovascular Systems, Inc. Antithrombogenic surface
US5591882A (en) * 1990-03-05 1997-01-07 Biocompatibles Limited Process for preparing organophosphates useful for increasing the ocular haemo- and biocompatibility of synthetic polymers
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US6251136B1 (en) 1999-12-08 2001-06-26 Advanced Cardiovascular Systems, Inc. Method of layering a three-coated stent using pharmacological and polymeric agents
US20090160074A1 (en) * 2007-12-20 2009-06-25 John Dallas Pruitt Method for making contact lenses
CN1957288B (zh) * 2004-05-24 2012-01-11 株式会社资生堂 防止蛋白质吸附的眼镜材料的制造方法
US20130041106A1 (en) * 2011-08-10 2013-02-14 Erin E. Carlson Chemoselective enrichment for compound isolation
US20140107328A1 (en) * 2011-08-10 2014-04-17 Indiana University Research And Technology Corporation Chemoselective enrichment for compound isolation
US9376385B2 (en) 2014-02-25 2016-06-28 Indiana University Research And Technology Corporation Solid-phase supports and uses thereof
CN110036016A (zh) * 2016-12-05 2019-07-19 日清纺控股株式会社 包含含有硅的磷酸阴离子的盐和润滑剂
WO2020100090A1 (fr) 2018-11-15 2020-05-22 Alcon Inc. Lentille de contact avec des alcools polyvinyliques modifiés par phosphorylcholine dans celle-ci

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ATE154023T1 (de) * 1990-11-05 1997-06-15 Biocompatibles Ltd Phosphorsäureester und ihre verwendung zur herstellung biokompatibler oberflächen
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JPH07505900A (ja) * 1992-04-24 1995-06-29 バイオコンパテイブルズ・リミテツド 金属皮膜
GB9301701D0 (en) * 1993-01-28 1993-03-17 Biocompatibles Ltd New zwitterionic materials
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WO1996029102A1 (fr) * 1995-03-17 1996-09-26 Regents Of The University Of Minnesota Materiaux biocompatibles
EP0790252A4 (fr) * 1995-08-31 1998-12-09 Nof Corp Derive d'acide fumarique et son polymere
WO1998055487A1 (fr) * 1997-06-04 1998-12-10 Biocompatibles Limited Composes de phosphate
JP4086305B2 (ja) * 2003-12-02 2008-05-14 株式会社資生堂 ホスホリルコリン基含有化合物及び該化合物からなる表面改質剤
JP3852942B2 (ja) * 2004-05-24 2006-12-06 株式会社資生堂 水中分散性化粧料用粉体
JP3715308B1 (ja) * 2004-05-24 2005-11-09 株式会社資生堂 眼用レンズ材料及びその製造方法
JP3715309B1 (ja) * 2004-05-24 2005-11-09 株式会社資生堂 眼用レンズ材料及びその製造方法
JP3738027B2 (ja) * 2004-05-24 2006-01-25 株式会社資生堂 蛋白質吸着防止眼用材料の製造方法
JP3715310B1 (ja) * 2004-05-24 2005-11-09 株式会社資生堂 蛋白質吸着防止眼用レンズ材料及びその製造方法
JP4191225B2 (ja) * 2007-01-18 2008-12-03 株式会社資生堂 表面改質方法及び表面改質材料
JP5142279B2 (ja) * 2008-08-20 2013-02-13 独立行政法人産業技術総合研究所 生体関連物質計測デバイス、人工臓器用表面修飾材料
US9567357B2 (en) 2011-06-24 2017-02-14 Biointeractions Ltd. Biocompatible, biomimetic ampholyte materials
WO2022043407A1 (fr) 2020-08-25 2022-03-03 Laouarem Yousra Compositions destinées au traitement des troubles neurologiques
KR20240124730A (ko) * 2023-02-09 2024-08-19 스마트바이오팜 주식회사 연속흐름공정을 이용하여 콜린알포세레이트를 제조하는 방법

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US5591882A (en) * 1990-03-05 1997-01-07 Biocompatibles Limited Process for preparing organophosphates useful for increasing the ocular haemo- and biocompatibility of synthetic polymers
US5217743A (en) * 1992-02-07 1993-06-08 Paradigm Biotechnologies Partnership Biomaterials of enhanced biocompatibility
US5342621A (en) * 1992-09-15 1994-08-30 Advanced Cardiovascular Systems, Inc. Antithrombogenic surface
US6251136B1 (en) 1999-12-08 2001-06-26 Advanced Cardiovascular Systems, Inc. Method of layering a three-coated stent using pharmacological and polymeric agents
CN1957288B (zh) * 2004-05-24 2012-01-11 株式会社资生堂 防止蛋白质吸附的眼镜材料的制造方法
US8092724B2 (en) 2007-12-20 2012-01-10 Novartis Ag Method for making contact lenses
US7780879B2 (en) 2007-12-20 2010-08-24 Novartis Ag Method for making contact lenses
US20090160074A1 (en) * 2007-12-20 2009-06-25 John Dallas Pruitt Method for making contact lenses
US8440735B2 (en) 2007-12-20 2013-05-14 Novartis Ag Method for making contact lenses
US20130041106A1 (en) * 2011-08-10 2013-02-14 Erin E. Carlson Chemoselective enrichment for compound isolation
US20140107328A1 (en) * 2011-08-10 2014-04-17 Indiana University Research And Technology Corporation Chemoselective enrichment for compound isolation
US9079983B2 (en) * 2011-08-10 2015-07-14 Indiana University Research And Technology Corporation Chemoselective enrichment for compound isolation
US9303059B2 (en) * 2011-08-10 2016-04-05 Indiana University Research And Technology Corporation Chemoselective enrichment for compound isolation
US9376385B2 (en) 2014-02-25 2016-06-28 Indiana University Research And Technology Corporation Solid-phase supports and uses thereof
CN110036016A (zh) * 2016-12-05 2019-07-19 日清纺控股株式会社 包含含有硅的磷酸阴离子的盐和润滑剂
WO2020100090A1 (fr) 2018-11-15 2020-05-22 Alcon Inc. Lentille de contact avec des alcools polyvinyliques modifiés par phosphorylcholine dans celle-ci
US11061169B2 (en) 2018-11-15 2021-07-13 Alcon Inc. Contact lens with phosphorylcholine-modified polyvinylalcohols therein

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US5091551A (en) 1992-02-25
DE3570673D1 (en) 1989-07-06
JPH0665266A (ja) 1994-03-08
US4937369A (en) 1990-06-26
WO1985003295A1 (fr) 1985-08-01
JPH06298778A (ja) 1994-10-25
JPH0665265A (ja) 1994-03-08
JPS61500918A (ja) 1986-05-08
GB8401534D0 (en) 1984-02-22
ATE43602T1 (de) 1989-06-15
JPH0665264A (ja) 1994-03-08
EP0157469A1 (fr) 1985-10-09
JPH0631273B2 (ja) 1994-04-27
JPH07114806B2 (ja) 1995-12-13
JP2648426B2 (ja) 1997-08-27
EP0157469B1 (fr) 1989-05-31

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